Browsing by Subject "Biphasic finite elements"
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Item A remotely operable convection-enhanced thermo-therapy catheter system for broad distribution of therapeutics in the brain(2021-05-03) Mehta, Jason Nitin; Rylander, Christopher Grady, 1978-; Longoria, Raul G; Rausch, Manuel K; Rossmeisl, Jr, John HGlioblastoma is a highly invasive brain tumor resulting in a mean survival of only 8 months even with aggressive treatment. Convection-enhanced delivery (CED) is an investigational therapy to treat glioblastoma that utilizes loco-regional drug delivery. However, standard CED has proven to result in inadequate drug volume dispersed (V [subscript d]) increasing the likelihood of tumor recurrence. This dissertation focuses on the refinement and design of the Convection-enhanced Thermo-therapy Catheter System (CETCS) and explores methods for further improving V [subscript d] utilizing the new drug delivery protocols made possible by CETCS. First, a new fiber optic microneedle device (FMD) fabrication method, solid fiber inside capillary (SFIC) FMD, and a modified fusion splicing (FS) method is presented with the goal of increasing light delivery efficiency. The modified FS FMD resulted in an increase in light transmission efficiency compared to previous prototypes. Next, we test the ability of constant flow rate, controlled catheter movement to increase V [subscript d] compared to stationary catheters in an agarose gel model. V [subscript d] for retraction and intermittent insertion was significantly higher than the stationary group. Following the results of the controlled catheter movement study, the value of constant pressure, controlled catheter movement was hypothesized. Constant pressure infusions were conducted with stationary, 0.25 mm/min, and a 0.5 mm/min catheters in agarose gel. The 0.25 mm/min and 0.5 mm/min retracting constant pressure catheters resulted in significantly larger V [subscript d] compared to any other group. In order to expand on these results, a computational framework for predicting V [subscript d], flow rate, and concentration gradients for pressure controlled and flow controlled infusions with controlled catheter movement was developed. Results indicated that movement of any kind appears to have marked advantage over a stationary catheter for both V [subscript d] and concentration distribution. Finally, the design for the CETCS hardware and software, excluding those of the CETCS MRI transmission system, is presented. The CETCS system has the ability to remotely operate 6 lasers, 6 syringe pumps, 6 individual microneedles, and the primary cannula of the arborizing catheter. Additionally, the software collects pressure sensor data, and the most recent revision has the capability of pressure controlItem An arborizing, multiport catheter for maximizing drug distribution in the brain via convection enhanced delivery(2018-08) Elenes, Egleide Yaneth; Rylander, Christopher Grady, 1978-; Rausch, Manuel K; Rossmeisl, John; Tunnell, James; Yankeelov, ThomasGlioblastoma (GBM) is a high-grade malignant glioma with a mortality rate that exceeds 95% despite over eight decades of medical research dedicated to improve outcomes. GBM is extremely difficult to treat and practically incurable with standard treatment involving surgical resection, radiation, concomitant and/or adjuvant chemotherapy. Therefore, convection enhanced delivery (CED) was developed to improve therapeutic outcomes. CED involves intraparenchymal delivery of drugs into diseased tissue via a small catheter. CED has proven to bypass the blood brain barrier and achieve better drug distribution than diffusion-based therapies. Nevertheless, the large volumes necessary to target entire tumors and peritumor volumes have been previously unachievable with currently-available catheters. This dissertation describes the development of a multiport, arborizing catheter designed specifically for improving drug distribution in the brain. The performance of early-stage arborizing catheter prototypes was compared to single-port catheters in infusion studies using agarose brain phantoms. Volume dispersed (V [subscript d]) and mean distribution ratios (V [subscript d] :V [subscript i]) were quantified and compared between the two catheters. The arborizing catheter produced higher V [subscript d] values; however, it did not exhibit the greatest V [subscript d] :V [subscript i], likely due to overlapping distribution volumes from the multiple individual ports. Following infusion in brain phantoms, a biotransport study of the arborizing catheter was conducted using a multiphasic finite element framework. The model was used to predict dispersion volume of a solute in a permeable hyperelastic solid matrix as a function of separation distance between adjacent ports. Results show that increasing port distance can increase V [subscript d]; however, infusion time also increases significantly with greater port distance. One way to mitigate increased infusion times is to employ higher infusion flow rates. Finally, the performance of improved arborizing catheters was compared to reflux-preventing single-port catheters in excised pig brains. CT scans were used to quantify V [subscript d] and V [subscript d] :V [subscript i] of infused iohexol (contrast-enhancing agent). The average volume dispersed for the arborizing catheter was 5.8 times greater than the single-port catheter. Mean distribution ratios for both catheters were similar. Using the multiple ports of the arborizing catheter, high V [subscript d] was achieved at a low infusion rate with negligible reflux. Given that previous attempts of CED reported poor drug distribution, the arborizing catheter may help overcome the limitations of CED.